|Budget Amount *help
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1989: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1988: ¥1,300,000 (Direct Cost: ¥1,300,000)
Although the mechanism of neural tissue damage in HTLV-I associated chronic myelopathy (HAM/TSP) remains virtually unknown, several lines of evidence suggest the involvement of a soluble factor(s) including cytokines and viral proteins in the disease process. In this study, we examined cytopathic effects of the supernatants from six HTLV-I carrier human T lymphocyte cell lines (MT-1, MT-2, TCL-Kan, TL-Mor, TL-Hir, and TL-Oml) on four human and one murine neuroblastoma cell lines (IMR-32, SK-N-SH, Togawa, NB1, and C-1300 clone NA), and two human glioma cell lines (Onda-11 clone 3 and U251MG). Among six lymphocyte cell culture supernatairits, only one from MT-2 cell culture repeatedly exerted cytopathic effects on human neuroblastoma cells, particularly on IMR-32 cells: marked cellular clumping and piling up. This activity was neither abolished by treatment of the medium at 80ﾟC for 30 min or by UV-irradiation, nor neutralized by anti-HTLV-I antibodies. The MT-2 supernatant also induced mild morphological changes in two other human neuroblastoma cell lines (SK-N-SH and Togawa) and two human glioma cell Iines. This activity was abolished by treatment of the medium at 80ﾟC for 30 min but not at 56ﾟC for 30 min. Myelinated murine cerebellum explants and other cell lines showed no morphological changes when incubated with the MT-2 supernatant. These observations suggest that HTLV-I induced cytokines may directly act on neural cells, and supports the possibility of the involvement of HTLV-I induced-lymphokines in the pathogenesis of retrovirus associated CNS disbases.